EPOCH and Rituximab to Treat Non-Hodgkin's Lymphoma in Patients With HIV Infection

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HIV-infected patients have a weakened immune system, and chemotherapy, which is used to treat lymphoma, probably causes further damage to the immune system.

Limiting the amount of immune damage due to chemotherapy might decrease the number of infections and the risk of developing cancer in the future in HIV-infected patients with non-Hodgkin's lymphoma.

Objectives:

To determine whether reducing the total amount of chemotherapy using a specific combination of drugs called EPOCH-R (etoposide, doxorubicin, vincristine, cyclophosphamide and rituximab) will rid the body of lymphoma quickly while decreasing the risk of infections and future cancers.

To determine whether the lymphoma will remain undetectable for at least one year if treatment is stopped one cycle after the patient enters remission.

Eligibility:

-Patients with non-Hodgkin's lymphoma and HIV infection 4 years of age and older who have not been treated previously with rituximab or cytotoxic chemotherapy.

Design:

Patients receive EPOCH-R in 3-week treatment cycles for at least three and no more than six cycles.

The lymphoma is evaluated using CT and PET scans at the end of treatment cycles 2 and 3. A bone marrow biopsy is repeated after cycle 2 if a biopsy was initially positive on screening for participation in the study.

Anti-HIV therapy is stopped before chemotherapy begins and is restarted when EPOCH-R treatment ends.

Patients are monitored for treatment response with blood tests and imaging scans at baseline, when treatment ends, 2 months after treatment ends and then every 3 to 6 months for a total of 24 months following chemotherapy.

Condition or disease

Intervention/treatment

Phase

Lymphoma, AIDS-relatedLymphoma, Large B-Cell, Diffuse

Biological: RituximabBiological: filgrastimDrug: EPOCH

Phase 2

Detailed Description:

Background:

This is a study to investigate in a preliminary fashion the feasibility of short course chemotherapy to patients with HIV-associated non-Hodgkin's lymphoma (HIV-NHL).

This study will investigate if the paradigm for treatment can be successfully changed from a standard of 6 cycles to one cycle beyond complete remission with 6 total allowable cycles.

Objective:

To assess with 90 percent probability that at least 50 percent of patients treated with short-course EPOCH-R will be progression free at one year.

Eligibility:

Aggressive CD20 positive DLBCL.

HIV+ serology.

All stages (I-IV) of disease.

ECOG Performance status 0-4.

NHL previously untreated with cytotoxic chemotherapy.

Age greater than or equal to 18 years.

May not be pregnant or nursing.

May not have received previous rituximab.

Design:

Patients will be treated every three weeks with a combination of EPOCH and rituximab for one cycle beyond CR/CRu by CT scan of all detectable tumors for a minimum of three and maximum of six cycles. Following cycle 2, CT, positron emission tomography scans (PET), and bone marrow biopsies (if initially positive) will be performed.

At the conclusion of the study, we will estimate whether the number of cycles can be reduced using the paradigm. If the cumulative number of patients to relapse exceeds 25 percent by 6 months, the study will be closed.

Following the completion of chemotherapy, restaging will be performed 2 months following the end of treatment, then every 3 months for one year, every 6 months for one year, then every 12 months until relapse, death, or loss to follow up.

Antiretroviral therapy (ART) will be given concurrently with treatment regimen.

To study the effects of treatment approach on parameters of HIV disease, measurements of CD4 cells and viral loads will be made at baseline and at the completion of therapy, and then 2 months following the end of treatment, and then every 3-6 months for a total of 24 months following chemotherapy.

Progression-free survival at 1 year after completion of study treatment [ Time Frame: Time of progressive disease ]

Disease progression as indicated by imaging scans and blood tests (CD4 cells and viral loads) at baseline, at the completion of therapy,2months following the end of treatment, and every 3-6 months (for a total of 24 months) following therapy.

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NHL previously untreated with cytotoxic chemotherapy; however, patients may be entered if they have had prior cyclophosphamide for an urgent problem at diagnosis (e.g. epidural cord compression, superior vena cava syndrome) and/or a single dose of intrathecal methotrexte (MTX) at the time of the pre-treatment diagnostic lumbar puncture

Creatinine less than or equal to 1.5 mg/dl or creatinine clearance greater than or equal to 50 ml/min

Bilirubin less than 2.0 mg/dl, or total bilirubin less than or equal to 4.5 mg/dl with direct fraction less than or equal to 0.3 mg/dl in patients for whom these abnormalities are felt to be due to protease inhibitor therapy

AST and ALT less than or equal to 3x ULN (AST and ALT less than or equal to 6x ULN for patients on hyperalimentation for whom these abnormalities are felt to be due to the hyperalimentation)

ANC greater than or equal to 1000/mm(3)

Platelet greater than or equal to 75,000/mm(3) (unless impairment due to ITP)

Ability of patient to provide informed consent.

EXCLUSION CRITERIA:

Previous rituximab

Pregnancy or nursing.

- Doxorubicin, etoposide, vincristine and cyclophosphamide are teratogenic and may be excreted in milk.

Current clinical heart failure or symptomatic ischemic heart disease.

Serious underlying medical condition or infection other than HIV that would contraindicate SC-EPOCH-R.